Dengue virus (DENV) infections of humans has steadily increased in importance as an emerging infectious disease, and the development of protective vaccines to DENV disease has been impeded by a lack of understanding of the specificity of virus-specific immune responses and their role in protection and disease. To address these critical issues related to DENV infection and disease, we have established a unique collaborative research consortium, US-Brazil Center for Immunology of Emerging Infectious Diseases (CIEID) that includes investigators from the University of Pittsburgh, Johns Hopkins School of Medicine, and the Laboratory of Virology and Experimental Therapy in Recife, Brazil. The focus of the CIEID is to conduct a comprehensive analysis of the immune responses to DENV infection of humans using the unique clinical samples obtained from the Clinical Core in Brazil to characterize the initial role of antigen presenting cells in DENV immunopathogenesis (Project 1), to define the interaction of T-lymphocyte with dendritic cells in the progression of immunity and disease (Project 2), to define how DENV suppresses innate immune responses to DENV infection (Project 3), and to define the specificity of common T-lymphocyte responses that are established to DENV infection. These translational immunology studies are complemented by a Technology Development Project designed to identify reliable biomarkers of DENV disease (Project 5), by a Pilot Projects Core to recruit new research areas and expertise, by a Virology Core to provide viral and molecular reagents, and by an Adminstrative Core to coordinate project activities and interactions with the CCHI Network Steering Committee. It is anticipated that the results of the proposed studies will produce important new insights into the role of DENV-specific immunity in infection and disease that can then inform strategies for treatment and vaccine development. In addition, it is expected that the US-Brazil CIEID will provide platform technologies and comprehensive expertise in translational immunology that can readily be applied to other emerging infections diseases or biodefense pathogens.